AUTHOR=Zhu Bingbing , Fang Ji , Ju Zhengcai , Chen Ying , Wang Li , Wang Hao , Xing Lina , Cao Aili 

TITLE=Zuogui Wan ameliorates high glucose-induced podocyte apoptosis and improves diabetic nephropathy in db/db mice

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.991976

DOI=10.3389/fphar.2022.991976

ISSN=1663-9812

ABSTRACT=Zuogui Wan (ZGW), a well-known traditional Chinese medicine (TCM), has been used to nourish “Kidney-Yin” for a long time in China, implying a protective effect on the kidney. The aim of the present study is to investigate the effect of ZGW on high glucose-induced podocyte apoptosis and diabetic nephropathy in db/db mice. ZGW (1g kg-1 day-1) was administered intragastrically to db/db mice for 8 weeks. HPLC was used for identifying the components of ZGW, biochemical and histopathological approaches were used for evaluating its therapeutic effects, and cultured mouse podocytes for further exploring its underlying mechanism in vitro. ZGW improved renal function, podocyte loss, and also normalized kidney reactive oxygen species production in db/db mice. The cytotoxicity of ZGW on mouse podocytes was assessed by LDH assay. The effect of ZGW on podocyte viability and apoptosis were determined with CCK-8 and Annexin-V/PI staining by treatment with high glucose. That ZGW attenuated podocyte apoptosis and oxidative stress were detected by the peroxide-sensitive fluorescent probe 2’,7’-dichlorodhydro-fluorescein diacetate (DCF-DA) staining, in a dose-dependent manner. Furthermore, ZGW decreased the expression of caspase-3 and phospho-p38 in both kidney cortex and high glucose-treated podocytes. Thus, our data from in vivo and in vitro studies demonstrated ZGW improved renal injury in diabetes by inhibiting oxidative stress and podocyte apoptosis.